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Advances and Limitations of Antibody Drug Conjugates for Cancer.

ABSTRACT: The popularity of antibody drug conjugates (ADCs) has increased in recent years, mainly due to their unrivalled efficacy and specificity over chemotherapy agents. The success of the ADC is partly based on the stability and successful cleavage of selective linkers for the delivery of the payload. The current research focuses on overcoming intrinsic shortcomings that impact the successful development of ADCs. This review summarizes marketed and recently approved ADCs, compares the features of various linker designs and payloads commonly used for ADC conjugation, and outlines cancer specific ADCs that are currently in late-stage clinical trials for the treatment of cancer. In addition, it addresses the issues surrounding drug resistance and strategies to overcome resistance, the impact of a narrow therapeutic index on treatment outcomes, the impact of drug-antibody ratio (DAR) and hydrophobicity on ADC clearance and protein aggregation.

SUBMITTER: Mckertish CM

PROVIDER: S-EPMC8389690 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Advances and Limitations of Antibody Drug Conjugates for Cancer.

Mckertish Candice Maria CM Kayser Veysel V

Biomedicines 20210723 8

The popularity of antibody drug conjugates (ADCs) has increased in recent years, mainly due to their unrivalled efficacy and specificity over chemotherapy agents. The success of the ADC is partly based on the stability and successful cleavage of selective linkers for the delivery of the payload. The current research focuses on overcoming intrinsic shortcomings that impact the successful development of ADCs. This review summarizes marketed and recently approved ADCs, compares the features of vari ...[more]

PMID: 34440076

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Project description:Background and objectiveTriple-negative breast cancer (TNBC) is more aggressive when compared with other breast cancer subtypes, and advanced TNBC (aTNBC) has always been a challenge for clinical treatment. In recent years, significant progress has been made in the research of antibody-drug conjugates (ADCs), especially targeting trophoblast cell-surface antigen 2 (TROP2), as an effective regimen to enhance the potential survival benefit and quality of life of relevant patients. The objective of this narrative review is to provide a comprehensive knowledge on latest progress of ADCs in the treatment of aTNBC. Furthermore, the clinical significance and future research directions for ADCs are also discussed.MethodsAs of December 2023, literature spanning the past decade was comprehensively searched and analyzed across PubMed, Wanfang Data, ClinicalTrials.gov, and relevant academic conferences, to identify the latest published literature or ongoing trials on ADCs for aTNBC. The selected literature primarily focused on the drug structural profile, pharmacological mechanism, important trials targeting different antigens, and other exploratory investigations.Key content and findingsThe advent of precision therapy has been facilitated by the new generation ADCs, which have demonstrated the capacity to prolong survival in patients with refractory aTNBC, and promote the research on molecular biological characteristics of aTNBC. Meanwhile, several clinical issues on treatment are emerging, including a detailed understanding of the clinical profile differences among specific ADCs, identification of the potential indications for ADCs, and management strategies for the adverse effects related to ADCs. Additionally, it is essential to clarify the clinical significance of the expression level of the target antigen for ADCs, to comprehend resistance mechanisms to ADCs, and to determine the optimal sequence of treatments between different ADCs. Furthermore, there is a need to investigate the potential of combination immunotherapy with ADCs. Up to date, the preliminary investigations on the aforementioned issues have been initiated, and further research will facilitate the enhancement of ADCs clinical utilization.ConclusionsThe use of ADCs has been recommended by various clinical guidelines, and significantly altering the landscape of treatment for aTNBC. Nevertheless, further investigation are required to determine the most effective use of ADCs.

Dataset Information

Advances and Limitations of Antibody Drug Conjugates for Cancer.

Publications

Advances and Limitations of Antibody Drug Conjugates for Cancer.

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